Separable capsule

ABSTRACT

The present disclosure relates to a separable hard capsule for containing a medication. The capsule may be opened by finger force and used, for example, by pediatric and geriatric patients.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.14/774,119, filed Sep. 9, 2015, which is the U.S. National Stage ofInternational Application No. PCT/IB2014/058948, filed Feb. 13, 2014,which was published in English under PCT Article 21(2), which in turnclaims the benefit of U.S. Provisional Patent Application No.61/821,753, filed on May 10, 2013, all of which are hereby incorporatedin their entireties, by reference.

DESCRIPTION

The present disclosure relates to a capsule for containing a medication,and more particularly, to a reopenable hard capsule. The capsule may beopened by hand and used, for example, by pediatric and geriatricpatients.

The recipient of an oral medication must be willing and able to swallowthe medication for proper administering. Medication prescribed for oralingestion is often manufactured and distributed in the form of a pill orwithin a capsule. Some pediatric and geriatric patients, however, may beunwilling or unable to swallow and ingest the pill or capsule. Thisdilemma is discussed in an article titled “Swallowing dysfunction anddysphasia is an unrecognized challenge for oral drug therapy,” by S.Stegemann, M. Gosch, and J. Breitkreutz, International Journal ofPharmaceutics, July 2012. The article highlights that swallowing issuesare an increasing problem of the aging population as they can adverselyaffect administration of oral medication.

An alternative to swallowing and ingesting a whole pill or capsule istaking the medication in powder or liquid form. This can include takinga medication out of a capsule, mixing the powder or liquid with food oradditional liquid, and eating or drinking the mixture. Eating themedication is possible if the medication is in liquid or solid form andcan be mixed with a food that is easily accepted by a patient, forexample, yogurt or custard. If the medication is in liquid form ordissolvable in a liquid, for example, water or juice, the patient maydrink the medication.

Medication in pill form can be difficult to dissolve in liquid or mix infood unless the pill is pulverized into smaller pieces or a powder.However, pulverizing a pill can be difficult for young or old patients,and a portion of the pill may be lost unintentionally, reducing the doseof medication.

In contrast to a solid pill, a capsule can contain medication in theform of a liquid, powder, granular material, solid, semi-solid, fibers,or combination of such forms. Rather than pulverizing a solid pill, acapsule may contain the medication in a state ready for mixing withliquid or food.

There are two main types of capsules, soft-shelled and hard-shelled.Soft-shelled capsules are primarily used for oils and active ingredientsthat are dissolved or suspended in oil. The soft shelled capsule istypically a single piece. Hard-shelled capsules are usually comprised oftwo pieces that are telescopically coupled together duringmanufacturing. However, standard hard capsules are not designed to bereopened once filled with the medication and fully closed after filling.

Examples of hard capsules include, for instance, a gelatin capsule suchas CONI-SNAP® capsule (commercially available from CAPSUGEL®), a cornstarch capsule, a hydroxypropyl methylcellulose capsule such as HPMCcapsules (commercially available from CAPSUGEL®, see VCAPS® and VCAPSPLUS® capsules), and pullulan-based capsules (commercially availablefrom CAPSUGEL®, see PLANTCAPS® capsules). Hard capsules can containdifferent volumes of medication depending on the length and diameter ofthe capsule. Capsules can come in standard and elongated sizes thatinclude Size No. 000, No. 00 No. 0, No. 1, No. 2, No. 3, No. 4, and No.5.

Standard medication or pharmaceutical hard capsules designed for oralingestion, for example, telescope-type capsules, consist of two parts, acap and a body. The cap is usually tubular or cylindrically shaped, witha closed end and open end. The body usually has a similar shape, butwith a slightly smaller diameter allowing telescopic insertion into thecap.

Some cap and body pieces are designed to be reopenable for filling orprocessing purposes. Typically, these cap and body pieces are coupledtogether in a “prelock” or “preclosed” condition in which the body partis at least partially located within the cap. The cap and body remaincoupled in the “prelock” condition until they are filled withmedication. Before filling, the two pieces are separated. The body isfilled with medication and then the two pieces are fully closed andlocked together.

Maintaining a suitable prelock condition can be problematic. On the onehand, the capsule parts should readily separate in the filling machine.Thus, a low prelock force is desirable. One the other hand, thepreclosed capsules must withstand transport to the filling apparatuswithout separation of the cap from body. This ideally requires a highprelock force. The variation of prelock force of individual capsulesshould be as low as possible to allow for predictable separation ofpieces. A capsule having suitable prelock force and/or prelock forcevariation is described in commonly assigned U.S. Pat. No. 5,769,267(“the '267 patent”), which is herein incorporated by reference in itsentirety. The two-piece hard capsule described in the '267 patent has aprelock force range of 10 grams to 30 grams.

The force needed to open a two-piece hard capsule from a closedcondition (including a prelocked condition) may be measured using aforce gauge. Thus, a two-piece hard capsule may be placed in a closedcondition and positioned in a holder. The holder secures the capsulesuch that one end may be rendered stationary. The cap and the body arethen separated in a controlled manner, e.g., by application of steadyforce along the longitudinal axis of the closed capsule. The forceneeded to achieve the separation is then recorded. Reasonable “finger”force for a capsule designed to be reopened ranges from about 30 gramsto about 200 grams, and may be from about 50 grams to about 150 grams.In some embodiments, the finger force for a capsule designed to bereopened range from about 100 grams to about 150 grams.

Similar to the prelock condition, the fully closed condition hasdesirable performance characteristics. For example, most medicationadministration involves capsules designed to remain fully closedindefinitely. However, some administration may require the capsule to bereopened, allowing the contents of the capsule to be sprinkled out andadministered in combination with a food or drink. Ideally, capsulesdesigned to be reopened should also remain fully closed in cases wherethe medication is to be administered in capsule form.

Current capsules configured to have prelocked and fully closed positionsgenerally have disadvantages associated with the opening force range orthe prelock force range, and sometimes both. For example, the '267patent capsule has a suitable prelock force range (i.e., about 10-30grams) for some uses, while exhibiting a relatively high opening force(i.e., about 400-800 grams). The high opening force may provide areliable fully-closed condition, but the opening force required toreopen can be too high. A person may not be able to apply enough forceto separate the two parts and reopen the capsule, or the applied forcewill break the capsule and waste the medication. Other capsule designsmay have a lower opening force range that allows a person to reopen thecapsule, but the opening force can be too low and therefore susceptibleto accidental separation of the capsule parts. Capsules lacking specificclosed position features or fixed closing or prelocked positions havevariations in closed or prelocked length, which can create issues inpackaging (i.e., blister packaging) and/or in printing. Additionally,current reopenable capsules configured to have prelocked and fullyclosed positions also have disadvantages associated with variation inthe prelocked or preclosed capsule length. Since modern filling andprocessing methods use automated processes to open prelocked capsules,variation in capsule geometry may adversely affect the uniformity of thefinal product. Additionally, variation in capsule geometry may result infailure to print radially; currently available reopenable capsules maybe limited in only being printable in an axial direction; upon aprinting trial of rectified radial printing (#00 print pockets and #0feed drum, engraved roll R9034, style 10×7), the capsules failed torectify in the feed drum, the print machine failed to run and the guidewire broke. Examples of such capsules are made by Capsugel and sold byNutra for veterinary applications; these capsules have only a singlelocking ring.

There are numerous patents directed towards locking hard capsules. Forexample, U.S. Pat. No. 3,399,803 describes a separation resistantcapsule which remains intact without unintended loosening ordislodgement of the cap from the body. In addition, the cap and bodyenter into a fully locked position. U.S. Pat. No. 3,823,843 describes amechanical lock position between the cap and body pieces of the capsulewhen the two pieces are completely telescoped together. U.S. Pat. No.4,040,536 describes tooth-like projections to lock the body and capagainst relative axial and rotational movement providing a reliable sealwhich is not broken when capsules are packaged, transported andsubsequently treated. U.S. Pat. No. 4,792,451 describes a capsulecomprising a cap and body circumferential slots for slidably locking ofcap and body members during final locking.

The '267 patent disclosed above describes optimized design parametersand increased SNAP-FIT® force design creating a permanent connection. Incontrast, some patents have designs directed to capsules or encapsulatedproducts that are openable and allow for sprinkling of the materialenclosed. For example, U.S. Pat. No. 4,076,848 discloses capsules foruse with pulverized dehydrated fruits and vegetables that contain smallamounts of the product. The capsules are designed to be easily openedand re-closed, in order to choose the desired amount of product. U.S.Pat. No. 5,587,177 discloses a capsule that is easily openable to allowfor removal of the contents, but this capsule is designed not to bere-closeable.

However, none of capsules disclosed in the foregoing documents have aprelock condition and a suitable opening force range. In order toovercome the limitations of the prior art, the present disclosuredescribes a hard capsule with an opening force range that allows aperson to reopen the capsule with finger pressure while still reliablymaintaining the closed position. The capsule may also have an acceptableprelock force range, low force variation, low variability in the lengthof the capsule in the prelock and closed conditions, and is able to befilled, processed, and printed on high speed automated capsule machines.

Such capsules can be readily used by pediatric and geriatric patients ifthey have more difficulty taking medication orally in pill or capsuleform. It is also understood that the capsule described by the presentdisclosure is not limited to use in the pediatric and geriatric fields.

SUMMARY

In accordance with an embodiment, a two-piece releasable hard capsulemay include a first part having an open end, a closed end, insertionaxis, and a first connection unit having a lock area comprising aplurality of first coupling elements. The two-piece releasable hardcapsule may also include a second part having a second connection unit.The second connection unit may have an engagement area comprising asecond coupling element, and the engagement area may be configured toengage with the lock area when the second part is fully inserted in thefirst part to form a connection releasable by a finger force. When thesecond part is fully inserted in the first part, in a fully closedposition, only the connection between the first coupling elements andthe second coupling element may provide a, typically mechanical, lockingforce holding the first and second parts together to form theconnection. The locking force may be less than the finger force. Theengagement area and the lock area may be arranged to engage withoutsubstantial deformation. The first coupling elements may compriseprotrusions substantially elongate in shape, typically all saidprotrusions being elongate in shape. The elongate protrusions maycomprise a restriction edge generally perpendicular to the insertionaxis, this may have the further advantage of ensuring a constant averagecapsule length (body plus cap), particularly when a pre-lock position isused, to further improve pocket fill rate in the manufacturing process(e.g. in printing of capsules). The second coupling element may comprisean indentation having a recessed ring that may extend along the entirecircumference of the second part, such may bring advantages such as easylocation of first and second parts upon locking as well as reduced riskof deflections on surfaces of the first and/or second parts.

In accordance with another embodiment, a two-piece releasable hardcapsule may include a first part having an open end, a closed end,insertion axis, and a first connection unit. The first connection unitmay include an inner wall defining a first cavity, a prelock area, and alock area. At least part of the lock area may be located between theprelock area and the closed end. The two-piece releasable hard capsulemay also include a second part having a second connection unit. Thesecond part may include an outer wall which is insertable into the firstcavity generally along the insertion axis through the open end; and anengagement area configured to engage with the prelock area when theouter wall is partially inserted in the first cavity to form a firstreleasable connection between the first part and the second part. Theengagement area may be configured to engage with the lock area when theouter wall is fully inserted in the first cavity to form a secondreleasable connection between the first part and the second part.

In a further embodiment, a two-piece releasable hard capsule may includea first part having an open end, a closed end, insertion axis, and afirst connection unit. The first connection unit may include a prelockarea and a lock area. The two-piece capsule may also include a secondpart having a second connection unit. The second connection unit mayinclude an engagement area. The first connection unit and secondconnection unit may be configured to form a first releasable connectionbetween the pre lock area and the engagement area and a secondreleasable connection releasable by finger pressure between the lockarea and the engagement area.

In any embodiment, the two-piece releasable hard capsule may be arrangedsuch that the area of contact between the lock area and the engagementarea is from 20% to 50%, preferably from 30% to 45%, of the totalsurface area of the engagement area (such may be the same also for thearea of contact between the first and second connection units). Thisarrangement may bring the advantage of ensuring sufficient locking forceto avoid unexpected and premature opening of the capsule (e.g. duringtransportation and handling) whilst at the same time, said force, stillbeing sufficiently low for a target subject to easily open the capsuleby applying pressure with one or more fingers to separate the first andsecond parts, when the content is to be poured out. The area of contactmay be measured by dividing the sum of the surface area of the lock area(e.g. the sum of the surface area of the plurality of coupling elements)and divide by the total surface area of the engagement area.

Certain embodiments include a method of using a two-piece releasablehard capsule for administering medication. The method may includeproviding a two-piece releasable hard capsule at least partially filledwith a medication. The method may further include applying a fingerforce to the two-piece releasable hard capsule to disengage a releasableconnection and separate the two-pieces of the capsule. In addition, themethod may include removing the medication from the two-pieces of thecapsule and combining the medication with at least one of a food or adrink to produce a mixture. Finally, the method may include providingthe mixture to a patient for consumption.

Additional objects and advantages of the present disclosure will be setforth in part in the description which follows, and in part will beobvious from the description, or may be learned by practice of thepresent disclosure. The objects and advantages of the present disclosurewill be realized and attained by means of the elements and combinationsparticularly pointed out in the appended claims.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the present disclosure, as claimed.

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate several embodiments of thepresent disclosure and together with the description, serve to explainthe principles of the present disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation showing a lateral view of atwo-piece hard capsule in accordance with one embodiment of the presentdisclosure (not to scale).

FIG. 2A, FIG. 2B, FIG. 2C, FIG. 2D, FIG. 2E, FIG. 2F, FIG. 2G, FIG. 2H,FIG. 2I, and FIG. 2J illustrate several protrusion geometries capable ofuse in embodiments of the present disclosure (not to scale).

FIG. 3 illustrates various design parameters of protrusions capable ofuse in embodiments of the present disclosure (not to scale).

FIG. 4 depicts an interval plot of force in grams to open various typesof capsules.

FIG. 5 depicts an interval plot of pre-closed length (PCL) inmillimeters of various types of capsules.

DETAILED DESCRIPTION

As used herein, reference to an element by the indefinite article “a” or“an” does not exclude the possibility that more than one of the elementis present, unless the context clearly requires that there is one andonly one element. The indefinite article “a” or “an” thus usually means“at least one.” The disclosure of numerical ranges should be understoodas referring to each discrete point within the range, inclusive ofendpoints, unless otherwise noted.

“Medication” includes any active ingredient, drug, supplement, ordietary supplement, including vitamins, proteins, peptides, nucleicacids, nutritional agents, and combinations thereof, and may be amedication or combination of medications selected from a variety ofknown classes including, but not limited to, analgesics,anti-inflammatory agents, anthelmintics, anti-arrhythmic agents,antibiotics (including penicillins), anticoagulants, antidepressants,antidiabetic agents, antiepileptics, antihistamines, antihypertensiveagents, antimuscarinic agents, antimycobactefial agents, antineoplasticagents, immunosuppressants, antithyroid agents, antiviral agents,anxiolytic sedatives (hypnotics and neuroleptics), astringents,beta-adrenoceptor blocking agents, blood products and substitutes,cardiac inotropic agents, corticosteroids, cough suppressants(expectorants and mucolytics), diagnostic agents, diuretics,dopaminergics (antiparkinsonian agents), haemostatics, immunologicalagents, lipid regulating agents, muscle relaxants, parasympathomimetics,parathyroid calcitonin and biphosphonates, prostaglandins,radiopharmaceuticals, sex hormones (including steroids), anti-allergicagents, stimulants and anorexics, sympathomimetics, thyroid agents, PDEIV inhibitors, NK3 inhibitors, CSBP/RK/p38 inhibitors, antipsychotics,vasodilators and xanthines. The medicine must be in a physicalformulation suitable for inclusion into a separable capsule, includingbut not limited to a powder or granulate formulation.

Embodiments as disclosed herein are designed for administration tohumans or other mammals.

It should be understood that the embodiments described herein are notlimited thereto. Those having ordinary skill in the art and access tothe teachings provided herein will recognize additional modifications,applications, embodiments, and substitution of equivalents that all fallwith the scope of the present disclosure. Accordingly, the presentdisclosure is not limited by the foregoing or following descriptions.

FIG. 1 shows a lateral view of a capsule 100 in accordance with oneembodiment of the present disclosure. Capsule 100 comprises a firstpart, namely cap 101, and a second part, namely body 102. Cap 101 andbody 102 each have an open end (103 and 104, respectively), a closed end(105 and 106, respectively), an inner wall (107 and 108, respectively),an outer wall (109 and 110, respectively), and a hollow cylindricallyshaped portion (111 and 112, respectively). Cap 101 and body 102 areadapted such that when aligned with insertion axis X with open ends 103and 104 facing each other, body 102 may be telescopically inserted intocap 101, thereby placing capsule 100 in a closed condition. When thecapsule is in a closed condition, a cavity is formed by inner walls 107and 108, the cavity being capable of holding a medicament or othercomposition. Outer wall 110 of body 102 may be configured to slideagainst inner wall 107 of cap 101 upon insertion of body 102 into cap101 by defining appropriate dimensions and/or using materials ofsufficient elasticity.

In the embodiment shown in FIG. 1, cap 101 further comprises a firstconnection unit 113 capable of engaging with a second connection unit114 located on body 102. The connection formed by the engagement of thefirst connection unit 113 and the second connection unit 114 isreleasable using typical human finger strength. The force needed torelease or disengage the first connection unit 113 from the secondconnection unit 114 may range from about 30 g to about 200 grams, orfrom about 50 grams to about 100 grams, or from about 100 grams to about150 grams, of force.

The first connection unit 113 may be integrally formed with the hollowcylindrically shaped portion 111 of cap 101. Thus, as shown in in FIG. 1the first connection unit 101 may be formed by shaping inner wall 107and/or outer wall 109. Similarly, the second connection unit 114 may beintegrally formed with the hollow cylindrically shaped portion 112 ofbody 102, and may be formed by shaping inner wall 108 and/or outer wall110. In this embodiment, the engagement of the first connection unit 113and the second connection unit 114 may be provided using the telescopicjoining of cap 101 and body 102—the frictional forces and/or mechanicalimpingements generated by the physical contact between the firstconnection unit and the second connection unit upon telescopic insertionof body 102 into cap 101 provide the resistance needed to preventcapsule 100 from opening spontaneously.

In certain embodiments of present disclosure, the engagement between thefirst connection unit 113 and the second connection unit 114 may beprovided in the following manner. As shown in FIG. 1, the firstconnection unit 113 may comprise a plurality of protrusions 115 arrayedalong the circumference of the first connection unit 113. Theprotrusions 115 may be arranged at regular or irregular intervals: thenumber of protrusions 115 may range from 2 to 10, for example 4 to 8, or4 to 6. The protrusions 115 may have a generally elongated shape, suchas an at least partially ellipsoidal or elliptical shape shown inFIG. 1. The elongated axis (axis of elongation) may be parallel toinsertion axis X. The latter arrangement may bring advantages not onlyto the manufacturing ease of capsules and respective pins but also inreducing the locking forces to an acceptable range such that opening byhand is simplified, such without impacting locking resistance duringhandling and transportation to limit accidental opening. The protrusionsmay extend inwardly into the cavity formed by inner wall 107, and may beformed, for example, by creating indentations in the hollowcylindrically shaped portion 111 of cap 101. The second connection unit114 may comprise a recessed ring 116 extending inwardly into the cavityformed by inner wall 108, which may be formed by creating acircumferential indention in the hollow cylindrically shaped portion 112of body 102. The depth of recessed ring 116 may range from about 30microns to about 85 microns. The second connection unit 114 may alsocomprise a tapering indentation 120 that provides a taper to recessedring 116. Thus, when body 102 is telescopically inserted into cap 101 toa sufficient degree or depth the protrusions 115 on cap 101 may engagewith the recessed ring 116 and/or tapering indentation 120 on body 102.

When the first connection unit 113 and the second connection unit 114are engaged by telescopic insertion of body 102 into cap 101, thecapsule 100 is in a locked or fully closed condition. To provide aprelocked or partially closed condition, cap 101 may comprise a thirdconnection unit (also referred to as a prelock connection unit) 117capable of engaging with the second connection unit 114. The thirdconnection unit 117 may lie between the first connection unit 113 andthe open end 103 of cap 101, and may be integrally formed with thehollow cylindrically shaped portion 111. The connection formed by theengagement of the third connection unit 117 and the second connectionunit 114 is releasable using forces on the order of those used bytypical automated capsule filling machines. The force needed to releaseor disengage the third connection unit 117 from the second connectionunit 114 may range from about 5 grams to about 35 grams, from about 10grams to about 30 grams, and from about 10 grams to about 25 grams, offorce.

In certain embodiments of the present disclosure, the engagement betweenthe third connection unit 117 and the second connection unit 114 may beprovided in the following manner. As shown in FIG. 1, the thirdconnection unit 117 may comprise a plurality of protrusions 119 arrayedalong the circumference of the third connection unit 117. Theprotrusions 119 may be arranged at regular or irregular intervals; thenumber of protrusions 119 may range from 2 to 10, for example 4 to 8, or4 to 6. The protrusions 119 may have a generally elongated shape, suchas ellipsoidal or elliptical shape shown in FIG. 1. The elongated axis(axis of elongation) may be parallel to insertion axis X. Theprotrusions 119 may extend inwardly into the cavity formed by inner wall107 and may be formed, for example, by creating indentations in thehollow cylindrically shaped portion 111 of cap 101. The secondconnection unit 114 may comprise a recessed ring 116 and taperingindentation 120, as discussed. Thus, when body 102 is telescopicallyinserted into cap 101 to sufficient degree or depth, the protrusions 119on cap 101 may engage with the recessed ring on 116 on body 102. Whenthe third connection unit 117 and the second connection unit 114 areengaged by telescopic insertion of body 102 into cap 101, the capsule100 is in a prelocked or partially closed condition. The protrusions 115may have a restriction edge generally perpendicular to the insertionaxis, and the restriction edge may be configured to restrict insertiondepth when inserting the body 102 into the cap 101 for engaging theprelock releasable connection.

To reduce the pressure build-up when placing the capsule 100 in a closedor prelock condition, body 102 may optionally comprise one or more vents118. Vents 118 provide indentations that facilitate the passage of airwhen body 102 is telescopically inserted into cap 101. Vents 118 may bearrayed along the circumference of the hollow cylindrically shapedportion 112 of body 102, and the indentions forming vents 118 may becontiguous with the indentation forming recessed ring 116. When one ormore vents are used, the protrusions 115 are arranged such that they arenot aligned with any one of the vents. By the term “not aligned” it isherein intended that an axis running through the centerline of theprotrusion along an insertion axis X does not run through the centerlineof the vent. The arrangement has the advantage of preventing lockingforce variation which may otherwise result in accidental opening of thecapsule during transportation and handling. Alternatively, the body 102may be free of vents 118, this may eliminate the need for ensuring thecap is correctly oriented with the body as described above. Optionally,the body may also have a ridge at the open end 104 to facilitateengagement during joining and closing.

Several protrusion geometries are capable of use as protrusions 115 orprotrusions 119. The individual protrusions of protrusions 115 orprotrusions 119 may have the same or different geometry. Exemplaryembodiments herein illustrated include: a lateral profile (FIG. 2A) anda cross-section view (FIG. 2B) of a “spherical” or “spheroid”protrusion; a lateral profile (FIG. 2C) and a cross-section view (FIG.2D) of a “cylindrical” protrusion; a lateral profile (FIG. 2E) and across-section view (FIG. 2F) of a cylindrical protrusion with anelongated flat region; a lateral profile (FIG. 2G) and a cross-sectionview (FIG. 2H) of a cylindrical protrusion with an elongated flat regionwith a single angled end; and a lateral profile (FIG. 2I) and across-section view (FIG. 2J) of a cylindrical protrusion with anelongated flat region with two angled ends.

Spherical or spheroidal protrusions and cylindrical protrusions may befurther described in terms of a radius R and depth D. A spherical,spheroidal, or cylindrical protrusion having radius R has a radius ofcurvature corresponding a sphere or cylinder having radius of the samelength as radius R. For spheroidal protrusions, including theellipsoidal or elliptical protrusions such those shown in FIG. 1, anadditional parameter such eccentricity may also further describe theprotrusion. Depth D is a measure of the degree of inward displacementfrom e.g. inner wall 107.

Variation in protrusion geometry may also be introduced using a flatregion and using different shapes for the protrusion ends, in particularpartially spherical, cylindrical or angled ends. Thus, as shown in FIG.3, a protrusion may be defined using radius R corresponding to theradius curvature of a partially spherical or cylindrical end, length Lof the flat region, angle A corresponding the angle formed by a flatend, and height H of the protrusion. Radius R may range from about 1.5millimeters to about 10 millimeters, e.g. from about 5 millimeters toabout 9 millimeters; length L may range from about 0 millimeters toabout 1 millimeter, e.g. from about 0 millimeters to about 0.5millimeters; angle A may range from about 0 degrees to about 90 degrees,e.g. from about 30 degrees to about 60 degrees; depth D may range fromabout 40 microns to about 200 microns, e.g. from about 100 microns toabout 180 microns; and height H may range from about 0.8 millimeters toabout 4 millimeters, e.g. about 2 millimeters to about 3 millimeters. Anexemplary embodiment of a protrusion in accordance with the presentdisclosure may comprise a partially spherical or cylindrical end and anangled end, wherein the angled end is between the partially spherical orcylindrical end and the open end of a capsule part, and the protrusionhas radius R of about 6.2 millimeters, length L of about 0.1millimeters, angle A of about 45 millimeters, depth D of about 160microns, and height H of about 2.3 millimeters.

Capsules in accordance with the present disclosure can be produced bymethods commonly applied for the production of telescope-type capsules,e.g., by means of dip molding processes with metal pins whose profileshave been made on the basis of the optimized parameters. Production bymeans of injection molding is possible. While the production oftelescope-type capsules for pharmaceutical or comparable applicationswhich make use of smaller capsule dip molding is currently preferred, itmay be advantageous for the production of larger containers made ofother materials to use injection molding or other suitable methods.

Capsules in accordance by the present disclosure may be produced fromvarious materials. For the production of smaller telescope-typecapsules, the outer skin of which is to disintegrate, e.g., in thedigestive tract or after they have been introduced into the mouth,gelatin, alginates, cellulose ester, methyl cellulose, cellulose etherester, acrylic resins, or substances having similar suitable propertiescan be used. Specifically, when injection molding methods are appliedfor the production of the capsules, use can be made also of starch.Various additives can be added, such as, e.g., glycerine, propyleneglycol, monoacetin, diacetin and triacetin, glycol diacetate, polyols,such as sugar or polyvinyl alcohol, gelatin, hydrophilic polymers,vegetable proteins, water-soluble polysaccharides, such as, e.g.,carrageenan or guar gum, blood proteins, egg proteins, acrylatedproteins, and others. Equally, dyestuffs and bactericides may be addedto telescope-type capsules. Other materials can be used as well, suchas, e.g., thermoplastic polymers.

The present disclosure may also be applied in capsules of all sizes,including standard and elongated sizes, such as e.g., Size No. 000, No.00 No. 0, No. 1, No. 2, No. 3, No. 4, and No. 5, for example, withdiameters from about 4 millimeters to about 14 millimeters, and lengthsfrom about 10 millimeters to about 30 millimeters. Certain embodimentsof the present disclosure are capsules of standard or elongated Size No.00 and 0. The capsules may range in diameter from about 4 millimeters toabout 14 millimeters. The length of the capsules may range from about 10millimeters to about 30 millimeters, particularly from about 11 to about27 millimeters.

Table 1 provides the parameters of various closing features tested forclosing force in FIGS. 4 and 5. Force to open is reported in grams offorce, and PCL in mm. The separable capsules tested were all standardsize #0 gelatin capsules formed by a dip molding process, with a closedlength of 21.7 millimeters and a pre-closed length (PCL) of 24.2millimeters. The external body diameter was 7.34 millimeters, with awall thickness of about 105 micrometers. The depth of the locking ringwas 55 micrometers. The tested capsules also had a ridge at the bodyedge to facilitate engagement.

Testing was performed at Capsugel, using a device incorporating acommercially available Shimpo digital force gauge. The body of thecapsule was fixed with a needle in the holder, and the force required toremove the cap was recorded. FIGS. 4 and 5 show the mean of each testwith error bars showing the 95% confidence interval.

Table 2 illustrates the average % fill of pockets in a printing machinebelt. The higher the % fill, the less empty pockets, resulting in higherthroughput of printed capsules. Numbers have been averaged over aprinting trial of 10,000 capsules. % fill are shown for capsules having(i) cap locking feature (i.e. plurality of first coupling elements) butfree of body locking feature (i.e. second coupling element) or (ii) acap locking feature (i.e. first coupling elements) and body lockingfeature (i.e. second coupling element).

TABLE 1 R D a L Type (mm) (μ) (°) (mm) Remark No feature NA Spherical45μ 8.65 45 NA Spherical 55μ 8.65 55 NA Spherical 65μ 8.65 65 NASpherical 100μ 8.65 100 NA Wide 65μ 8.65 65 NA Shape adapted to increaseindent's width around part's circumference Angle 75μ 6.2 75 75 0.5 Angle90μ 6.2 90 75 0.5 Steep angle 75μ 6.2 75 45 0.7 Steep angle 90μ 6.2 9045 0.7 Steep angle 120μ 6.2 120 45 0.1 Steep angle 140μ 6.2 140 45 0.1Steep angle 160μ 6.2 160 45 0.1

TABLE 2 Type % fill rate Cap locking feature + <75% No Body lockingfeature Plurality of coupling elements on >98% cap as locking feature +Body locking feature (recess)

Other embodiments of the present disclosure will be apparent to thoseskilled in the art from consideration of the specification and practiceof the present disclosure. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the present disclosure being indicated by the following claims.

We claim:
 1. A two-piece releasable hard capsule comprising: a firstpart having an open end, a closed end, insertion axis, and a firstconnection unit having a lock area comprising a plurality of firstcoupling elements; a second part having a second connection unit,wherein the second connection unit has an engagement area comprising asecond coupling element, the engagement area being configured to engagewith the lock area when the second part is fully inserted in the firstpart in a fully closed position, forming a locked connection, whereinthe locked connection is releasable by a finger force, wherein theplurality of first coupling elements comprise protrusions elongate inshape comprising an elongated axis running parallel to an insertion axisand comprising a restriction edge perpendicular to the insertion axis.2. A capsule according to claim 1, wherein the finger force is betweenabout 30 grams and about 200 grams.
 3. A capsule according to claim 1,wherein the second coupling element comprises an indentation having arecessed ring, wherein the recessed ring has an asymmetric cross-sectionalong the insertion axis.
 4. A capsule according to claim 1, wherein thefirst coupling elements have a depth of about 50 microns to about 200microns.
 5. A capsule according to claim 1, wherein the first connectionunit further comprises a prelock area comprising a plurality of thirdcoupling elements, and wherein the engagement area is configured toengage with the prelock area when the second part is partially insertedin the first part to form a prelock releasable connection.
 6. A capsuleaccording to claim 1, wherein the restriction edge is configured torestrict insertion depth when inserting the second part into the firstpart for engaging a prelock releasable connection.
 7. A two-piecereleasable hard capsule comprising: a first part having an open end, aclosed end, insertion axis, and a first connection unit comprising: aninner wall defining a first cavity; a prelock area; and a lock area,wherein at least part of the lock area is located between the prelockarea and the closed end; and a second part having a second connectionunit comprising: an outer wall which is insertable into the first cavityalong the insertion axis through the open end; and an engagement areaconfigured to engage with the prelock area when the outer wall ispartially inserted in the first cavity to form a first releasableconnection between the first part and the second part, and wherein theengagement area is configured to engage with the lock area when theouter wall is fully inserted in the first cavity in a fully closedposition forming a locked connection, wherein the locked connection is asecond releasable connection between the first part and the second part,preferably wherein the first releasable connection requires a firstforce to release and the second releasable connection requires a secondforce to release, preferably wherein the ratio of the first force tosecond force is from about 0.1 to about 0.2, wherein the prelock areacomprises a plurality of first coupling elements, the lock areacomprises a plurality of second coupling elements, and the engagementarea comprises a third coupling element, wherein at least one of thesecond coupling elements has a restriction edge perpendicular to theinsertion axis, wherein the restriction edge is configured to restrictinsertion depth when inserting the second part into the first part andengaging the first releasable connection, and wherein at least one ofthe plurality of first coupling elements and the plurality of secondcoupling elements comprises a protrusion having an elongated shapecomprising an elongated axis running parallel to an insertion axis andcomprising a restriction edge perpendicular to the insertion axis.
 8. Acapsule according to claim 7, wherein the first force is between about10 grams to about 30 grams.
 9. A capsule according to claim 7, whereinthe plurality of second coupling elements are located farther from theopen end than the plurality first coupling elements, wherein alongitudinal axes of the plurality of first coupling elements and theplurality of second coupling elements is parallel to the insertion axis.10. A capsule according to claim 7, wherein the third coupling elementcomprises an indentation having a recessed ring.
 11. A method of using atwo-piece releasable hard capsule according to claim 1 for administeringmedication, comprising: providing the two-piece releasable hard capsuleof claim 1 at least partially filled with a medication; applying afinger force to the two-piece releasable hard capsule to disengage areleasable connection and separate the two pieces of the capsule;removing the medication from the two-pieces of the capsule and combiningthe medication with at least one of a food or a drink to produce amixture; and providing the mixture to a patient for consumption.
 12. Acapsule according to claim 1, wherein the area of contact between thelock area and the engagement area is from about 20% to about 50% of thetotal surface area of the engagement area.
 13. A capsule according toclaim 1, wherein the first coupling elements have a depth of about 75microns to about 160 microns.
 14. A capsule according to claim 1,wherein the finger force is between about 100 grams and about 150 grams.15. A capsule according to claim 1, wherein the finger force is betweenabout 50 grams and about 150 grams.
 16. A capsule according to claim 1,wherein the first connection unit further comprises a prelock areacomprising a plurality of third coupling elements, and wherein theengagement area is configured to engage with the prelock area when thesecond part is partially inserted in the first part to form a prelockreleasable connection and wherein the plurality of third couplingelements have a depth of about 40 microns to about 90 microns.
 17. Acapsule according to claim 16, wherein the prelock release connection isreleased by a force of about 10 grams to about 30 grams.
 18. A capsuleaccording to claim 10, wherein the recessed ring has an asymmetriccross-section along the insertion axis.
 19. The method of claim 11,wherein the two-piece releasable hard capsule is configured to form aprelock connection that is released prior to filling of the capsule, andfollowing filling of the capsule the two pieces are reattached and thereleasable connection is formed.